While not born into a hereditary leadership role within the Iroquois League, Brant rose to prominence due to his education, abilities and his connections to British officials. His sister, Molly Brant, was the consort of Sir William Johnson, the influential British Superintendent of Indian Affairs in the province of New York. During the American Revolutionary War, Brant led Mohawk and colonial Loyalists known as "Brant's Volunteers" against the rebels in a bitter partisan war on the New York frontier. He was accused by the Americans of committing atrocities and given the name "Monster Brant", but the accusations were argued by later historians to have been false.

In 1784, Frederick Haldimand granted Joseph Brant and his followers a land treaty to replace what they had lost in New York State at the Sandusky Council after the Revolution. This tract, the Haldimand Grant, was about 833,333 hectares (2,000,000 acres) in size, covering the Grand River area in what is now southwestern Ontario "from the source to the mouth of the river and 9.6 kilometres (6 miles) deep on each side". The grant was later rescinded. Chief Brant relocated with most of his people to Upper Canada to the area which is now Six Nations Reserve, where he remained a prominent leader.

Joseph was born in March 1743, in the Ohio Country somewhere along the Cuyahoga River. This was during the hunting season when the Mohawk traveled to the area from Kanienkeh ("the Land of the Flint", the Mohawk name for their homeland in what is now upstate New York). He was named Thayendanegea, which in the Mohawk language can mean "two wagers (sticks) bound together for strength", or possibly "he who places two bets." As the Mohawk were a matrilineal culture, he was born into his mother's Wolf Clan. The Haudenosaunee League, of which the Mohawks were one of the Six Nations, was divided into clans headed by clan mothers. Growing up in a society where the chief political figures were the clan mothers gave Brant a respect for women that many Europeans considered odd in the 18th century, but seems very "modern" today. Anglican Church records at Fort Hunter, New York, noted that his parents were Christians and their names were Peter and Margaret Tehonwaghkwangearahkwa. His father died when Joseph was born. One of Brant's friends in later life, John Norton, wrote that Brant's parents were not born Iroquois, but were rather Hurons taken captive by the Iroquois as young people; the Canadian historian James Paxton wrote this claim was "plausible" but "impossible to verify", going on to write that this issue is really meaningless as the Iroquois considered anybody raised as an Iroquois to be Iroquois, drawing no line between those born Iroquois and those adopted by the Iroquois.

After his father's death, his mother Margaret (Owandah), the niece of Tiaogeara, a Caughnawaga sachem, returned to the province of New York from Ohio with Joseph and his sister Mary (also known as Molly). Molly Brant may actually been Brant's half-sister rather than his sister, but in Mohawk society, they would have been considered full siblings as they shared the same mother. They settled in Canajoharie, a Mohawk village on the Mohawk River, where they had lived before. The Mohawk in common with the other nations of the Haudenosaunee League had a very gendered understanding of social roles with power divided by the male sachrems and chiefs and the clan mothers (who always nominated the male leaders) with decisions reached by consensus between the clan mothers and the chiefs. Mohawk women did all farming (considered woman's work), growing the "Three Sisters" of beans, corn, and squash while men went hunting and engaged in diplomacy and wars. In the society that Brant grew up, there was an expectation that he would be a warrior as a man. .

In the part of the New York frontier where Brant grew up, the area had been settled in the early 18th century by immigrants from the Palatine in what is now Germany known as the Palatines. Relations between the Palatines and Mohawks were friendly with many Mohawk families renting out land to be farmed by the hard-working immigrants (though Mohawk elders complained that their young people were too fond of the beer brewed by the Palatines), and Brant grew up in a multicultural world surrounded by people speaking Mohawk, German and English. Paxton wrote that Brant self-identified as Mohawk, but as someone who grew with the Palatines, Scots and the Irish living in his part of Kanienkeh, the world that he grew up in was not entirely Mohawk, which explains why he was so comfortable with aspects of European culture. The common Mohawk surname Brant was merely the Anglicized version of the common German surname Brandt.